Catalyzed addition of acid chlorides to alkynes by unmodified nano-powder magnetite: Synthesis of chlorovinyl ketones, furans, and related cyclopentenone derivatives in memory of Professor Robert E. Gawley

Article abstract of DOI:10.1016/j.tet.2013.06.041

Inexpensive and commercially available nano-powder magnetite is an excellent catalyst for the addition of acid chlorides to internal and terminal alkynes, yielding the corresponding chlorovinyl ketones in good yields. The process has been applied to the synthesis of 5-chloro-4-arylcyclopent-2-enones, 3-aryl-1H-cyclopenta[a]naphthalen-1-ones, and (E)-3-alkylidene-2,3-dihydro-1H- cyclopenta[a]naphthalen-1-ones, just by changing the nature of the starting acid chloride or the alkyne. All tested processes elapse with an acceptable or excellent regio- and stereo-selectivity. Moreover, the use of the iridium impregnated on magnetite catalyst permits the integration of the chloroacylation process with a second dehydrochlorination-annulation process to yield, in one-pot, 1-aryl-2,4-dialkylfurans in good yields, independently of the nature of the starting reagents, and including the heteroaromatic ones.

Full text of DOI:10.1016/j.tet.2013.06.041

Tetrahedron 69 (2013) 7056e7065
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Catalyzed addition of acid chlorides to alkynes by unmodified
nano-powder magnetite: synthesis of chlorovinyl ketones, furans,
and related cyclopentenone derivatives
*
ꢀ
Rafael Cano, Miguel Yus, Diego J. Ramon
ꢀ
ꢀ
Instituto de Síntesis Organica (ISO) and Departamento de Química Organica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, E-03080 Alicante,
Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Inexpensive and commercially available nano-powder magnetite is an excellent catalyst for the addition of
acid chlorides to internal and terminal alkynes, yielding the corresponding chlorovinyl ketones in good
yields. The process has been applied to the synthesis of 5-chloro-4-arylcyclopent-2-enones, 3-aryl-1H-
cyclopenta[a]naphthalen-1-ones, and (E)-3-alkylidene-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-ones,
just by changing the nature of the starting acid chloride or the alkyne. All tested processes elapse
with an acceptable or excellent regio- and stereo-selectivity. Moreover, the use of the iridium
impregnated on magnetite catalyst permits the integration of the chloroacylation process with a second
dehydrochlorinationeannulation process to yield, in one-pot, 1-aryl-2,4-dialkylfurans in good yields,
independently of the nature of the starting reagents, and including the heteroaromatic ones.
Ó 2013 Elsevier Ltd. All rights reserved.
Received 21 January 2013
Received in revised form 3 June 2013
Accepted 12 June 2013
Available online 26 June 2013
In memory of Professor Robert E. Gawley
Keywords:
Acid derivatives
Alkynes
Heterogeneous catalysis
Ketones
Magnetite
Iridium
1. Introduction
their inherent toxicity, their handling difficulty, their instability,
high price, the CO extrusion from reagents depending on the cat-
The design of catalysts able to perform the heteroatom-
acylation of alkynes, forming in a regio-, stereo-selective and si-
multaneous manner a carbonecarbon and a carboneheteroatom
bonds, is extremely challenging.1 The interest of this reaction is not
only a matter of the intrinsic process but also of the final products.
alyst, and their no-reactivity with internal alkynes.
Very recently, different iron salts (FeBr29 and FeCl310) have been
introduced as a convenient, inexpensive, environmentally friendly,
and practical catalyst alternative. In our ongoing project on the use
of magnetite as an efficient catalyst for different organic reactions,11
we anticipated that it could be a new and sustainable alternative for
this process. Herein, we wish to describe its use as valuable catalyst
for the addition of acid chlorides to poor reactive internal alkynes
leading to the formation of chlorovinyl ketones, cyclopenta[a]
naphthalen-1-ones, 5-chloro-4-arylcyclopent-2-enones, and 2,3,5-
trisubstituted furans, depending on the nature of the substrates.
Thus, the addition of acid chlorides to alkynes gives b-chlorovinyl
ketones,2 which are a class of compounds very useful for the syn-
thesis of a variety of other compounds.
The initial use of stoichiometric amounts of aluminum de-
rivatives, as Lewis acids, for the FriedeleCrafts addition of acyl
chlorides to alkynes showed a very low selectivity, with the E-iso-
mer being the major product.3 The replacement of the aluminum
catalyst to silver perchlorate,4 gallium trichloride,5 or zinc oxide6
did not change so much the initial picture of this process. This
fact favored the introduction of typical transition metal complexes,
such as those derived from rhodium7 or iridium.8 These new
complexes permitted the reduction of the catalyst amount from
stoichiometric to 5e1 mol %, obtaining only the Z-chlorovinyl ke-
tone isomer. However, these catalysts have new drawbacks, such as
2. Results and discussion
2.1. Chloroacylation process
Since the reaction with internal alkynes is either unknown using
rhodium, iridium, gallium trichloride, and iron dibromide de-
rivatives or yields a very low isomeric ratio for the iron trichloride-
catalyzed reaction10 (with the E/Z ratio being 2.2/1), the addition of
benzoyl chloride (1a) to dec-5-yne (2a) was chosen as model
(Table 1). The first trial was carried out in absence of any catalyst to
* Corresponding author. Tel.: þ34 965903986; fax: þ34 965903549; e-mail ad-
ꢀ
dress: djramon@ua.es (D.J. Ramon).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.041

R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
7057
Recently, we have developed a new, simple, and robust method
to immobilize different transition metal oxides onto micro-
particles of magnetite,12 and we studied these catalysts, as well as
new ones, such as rhodium, silver, tungsten, and gold derivatives
(see Supplementary data) as possible promoters of the process.
However, in all cases the results (Table 2) were similar to those
obtained using only the magnetite support (entry 1).
Table 1
Optimization of the reaction conditionsa
Table 2
Optimization of the catalysta
Entry
Cat. (mol %)
T (ꢀC)
Solvent
t (h)
3a (%)b
4a (%)b
1
2
3
4
5
6
7
8
70
70
70
70
70
70
110
25
70
70
70
70
70
70
70
70
70
70
70
70
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
d
7
0
62
72
83
64
66
55
44
73
59
61
0
0
20
19
11
18
16
22
23
21
13
21
0
Fe3O4c (65)
Fe3O4d (65)
Fe3O4d (33)
Fe3O4d (13)
Fe3O4d (130)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
Fe3O4d (33)
FeO (33)
0.25
0.25
0.25
0.25
0.25
0.25
7
0.25
0.25
0.25
0.25
0.25
0.25
0.25
0.25
1
Entry
Catalyst (mol %)
3a (%)b
4a (%)b
9e
10f
11
12
13
14
15
16
17
18
19
20
1
2
3
4
5
6
7
Fe3O4c (65)
CoOeFe3O4 (1.4)
NiOeFe3O4 (1.4)
CuOeFe3O4 (1.3)
Ru2O3eFe3O4 (1.4)
Rh2O3eFe3O4 (0.8)
PdOeFe3O4 (1.4)
62
56
58
64
64
58
8
20
18
29
24
23
26
4
Dioxane
MeCN
DMF
CHCl3
(ClCH2)2
PhMe
PhMe
PhMe
PhMe
0
0
0
0
61
60
24
74
20
69
28
30
8
21
8
8
9
Ag2O/AgeFe3O4 (1.3)
WO3eFe3O4 (0.6)
IrO2eFe3O4 (0.14)
PtO/PtO2eFe3O4 (0.6)
Au2O3/AueFe3O4 (0.1)
NiO/CuOeFe3O4 (0.9/1.1)
PdO/CuOeFe3O4 (1.5/0.8)
66
66
67
59
65
60
9
20
16
19
17
21
25
6
Fe2O3 (33)
FeCl2 (33)
FeCl3 (33)
0.25
1
0.25
10
11
12
13
14
24
a
Reaction carried out using 1a (1.5 mmol) and 2a (1.0 mmol) in the corre-
sponding solvent (2.5 mL) under an argon atmosphere.
b
Isolated yield after column chromatography.
Powder<5 mm.
Powder<50 nm.
Reaction performed using 1a (2 mmol) and 2a (1.0 mmol).
Reaction performed using 1a (1.0 mmol) and 2a (2.0 mmol).
a
Reaction carried out using 1a (1.5 mmol) and 2a (1.0 mmol) in toluene (2.5 mL)
c
under an argon atmosphere.
d
e
f
b
Isolated yield after column chromatography.
Powder<5 mm.
c
As the nano-particle of magnetite was the best catalyst, the
scope of the reaction was studied (Table 3). The reaction gave the
expected Z-isomers 3 as the main product after only a 1 h reaction.
The reaction gave similar results independently of the side chain of
internal alkyne (entries 1e3). In the case of using ethynylbenzene
prove the real activity of iron oxide (entry 1), and after several
hours the reaction failed recovering the unchanged alkyne 2a.
However, a similar reaction but conducted in the presence of
a substoichiometric amount of micro-particles of magnetite (65% of
the stoichiometric gram atomic mass of iron) gave a mixture of
isomers (Z)-3a and (E)-4a after only 15 min at 70 ꢀC (entry 2). Both
isomers could be isolated by column chromatography and fully
characterized. Once the activity of unmodified commercial mag-
netite was proved, the size of the particles was tested, finding that
the related nano-particle gave even better yield and Z/E ratio (3.8/1,
entry 3). Then, the influence of the amount of catalyst was studied
(entries 3e6), as well as the temperature (entries 6e8), the re-
agent’s ratios (entries 9 and 10), and the solvent (entries 11e16),
with the best condition being described in the entry 4.
Table 3
Preparation of b
-chlorovinyl ketonesa
Entry
R1
R2
R3
Z/E ratiob
No.
Yield (%)c
nBu
Et
nBu
Et
7.5/1
7.5/1
5.7/1
>20/1
3.5/1
3.5/1
15/1
2.2/1
15/1
4.1/1
4/1
3a
3b
3c
3d
3e
3f
3g
3h
3i
83
89
82
63
70
75
91d
58
89
74
72
77
After finding the activity of nano-particles of magnetite, we
studied the activity of other iron sources, such as iron(II) and (III) as
catalyst (entries 17 and 18), with nano-particles of Fe2O3 having
a similar activity to magnetite. The necessity of a slight excess of acyl
chloride to complete the reaction made us suspect that the mag-
netite function was to form a soluble iron chloride species, and to
prove this fact we performed the reaction using FeCl2 and FeCl3,
and, as in the case of oxides, the iron(III) salt gave a better result
than iron(II). However, the results were significantly inferior to that
obtained using magnetite (compare entries 4, 19, and 20), and with
the price of iron chloride being also another small disadvantage. It
should be pointed out that the recycled magnetite had a lower ac-
tivity rendering, in a second trial, a mixture of compounds in lower
yield (72%), and dropping to 47% in the third run. To understand this
fact, we studied by ICP-MS analysis the resulting reaction solution
mixture after the first cycle, finding that 1.1% of initial amount of
iron of the catalyst was leached to the solution. This leaching phe-
nomenon could explain the decrease of the obtained yield.
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
nC5H11
H
nC5H11
Ph
4-ClC6H4
nBu
nBu
nBu
nBu
nBu
nBu
Ph
nBu
nBu
nBu
nBu
nBu
nBu
Ph
4-tBuC6H4
4-MeOC6H4
2-MeOC6H4
e
9
4-FC10H6
10
11
12
2-Thienyl
4-MeOC6H4
Ph(CH2)2
3j
3k
nBu
nBu
3/1
3lf
a
Reaction carried out using 1 (1.5 mmol) and 2 (1.0 mmol) in toluene (2.5 mL)
under an argon atmosphere.
b
Determined by 1H NMR from the crude mixture.
Isolated yield after column chromatography.
The relate indenone derivative was detected from the crude reaction medium
c
d
by GCeMS (<3%).
e
4-FC10H6 denotes for 4-fluoronaphth-1-yl.
The compound 3l could not be separated from the mixture of both isomers (Z)-
f
3l/(E)-3l.

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R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
Table 4
(entry 4) practically only one regio- and stereo-isomer was ob-
tained, as it was previously found for other ruthenium, iridium or
iron complexes. The presence of electron-withdrawing or electron-
donating groups at the para-position of aromatic ring did not have
a significant effect on the results (entries 5e7). However, the
presence of a group located at ortho-position (entry 8) of the acid
chloride gave worse results, in terms of chemical yield and isomeric
ratio. This fact could be a proof of a possible steric hindrance in the
transition state. Other acyl derivatives, such as 4-naphthyl or
thienyl, were used without finding any difference with the model
reagents (compare entries 1, 9, and 10). The reaction of 4-
methoxybenzoyl chloride with 1,2-diphenylethyne gave the ex-
pected product 3k (entry 11). It should be pointed out that the
reaction using aliphatic 3-phenylpropanoyl chloride gave the ex-
pected mixture of products (Z)-3l and (E)-4l, with the main isomer
3l not being possible to be separated from the isomer 4l; contrary
to other aromatic examples, in which isomer 3 could be isolated but
not the related 4.
Preparation of 5-chloro-4-arylcyclopent-2-enonesa
Entry
Catalyst
X
R1
R2
No.
Yield (%)b
1
2
3
4
5
6
7
8
Fe3O4
Fe3O4
Fe3O4
FeO
Fe2O3
FeCl2
FeCl3
Fe3O4
Fe3O4
H
H
H
H
H
H
H
H
nBu
nBu
nBu
nBu
nBu
nBu
nBu
Et
nBu
nBu
nBu
nBu
nBu
nBu
nBu
Et
8a
8a
8a
8a
8a
8a
8a
8b
8c
8d
8e
8f
78
77
58
29
67
34
69
89
91
91f
67
83
c,d
c
c,e
c
nC5H11
Me
nC5H11
tBu
c
9
H
H
F
c
The above protocol could beused notonly foracyl chlorides (1) but
also for the related bromides. Thus, the addition of benzoyl bromide
(5) to dec-5-yne (2a) using nano-particles of magnetite (Scheme 1)
gave the expected bromovinyl ketone 6, with similar yield and iso-
meric ratio to the case of using the related chlorine reagent.
10
11
12
Fe3O4
Fe3O4
Fe3O4
nBu
nBu
nBu
nBu
c
c
MeO
a
Reaction carried out using 7 (1.5 mmol) and 2 (1.0 mmol) in toluene (2.5 mL)
under an argon atmosphere.
b
Isolated yield after column chromatography.
Power<50 nm.
Reaction performed using 33 mol %.
Reaction performed using 7 mol %.
Mixture of isolated isomers (cis-8d/trans-8d0: 3/88%).
c
d
e
f
After the success in the cyclization process, we rationalized that
the stabilization of the vinyl cation intermediate could give us
a chance to carry out an intramolecular aromatic electrophilic
substitution, yielding fused bicyclic ketones.3c,7a For this purpose,
we carried out the model reaction of 2-naphthalenecarbonyl
chloride (1j) with the unsymmetrical 1-phenylpentyne (9a) and,
after only one hour, the corresponding 3-phenyl-2-methyl-1H-
cyclopenta[a]naphthalen-1-one (10a) was obtained in excellent
yield and regioselectivity (entry 1 in Table 5), with the other
regioisomer not being detected. The structure of compounds 10
was unambiguously assigned according to NOESY, HSQC- and
HMBC-NMR experiments, as well as X-ray data for compound 10a
(see Fig. 1). The reaction with other 1-arylalkynes gave, in all cases,
the corresponding products 10 (entries 2 and 3) with the reaction
pathway starting with the regioselective addition of acyl cation to
form the most stable 1-arylvinyl cation.
Scheme 1. Preparation of a b-bromovinyl ketone.
2.2. Nazarov-type cyclization processes
The mechanistic considerations of this reaction have proposed
the formation of a vinyl cation3c,4,5,10 intermediate, which is cap-
tured by the chloride ion through an intra- or intermolecular pro-
cess. With this proposed catalytic mechanism in mind, we thought
that the cationic intermediate could be trapped to form a cyclic
compound by using the adequate olefinic reagent in a Nazarov-type
process.13 So, the reaction of the alkyne 2a with cinnamoyl chloride
(7a, X¼H) yielded, after only one hour at 70 ꢀC, the expected 5-
chlorocyclopent-2-enone 8a in good yield and as a single isomer
(Table 4, entry 1).
Table 5
Preparation of 3-aryl-1H-cyclopenta[a]naphthalen-1-onesa
Then, we studied the influence of the amount of nano-
magnetite (entries 1e3), the source of iron oxides (entries 4 and
5), and different iron chlorides (entries 6 and 7). As in the case of
the chlorovinylation process, nano-magnetite gave even better re-
sults than iron(III) oxide or chloride. The reaction was performed
with similar results with other symmetrically substituted alkynes
(entries 8 and 9). In the case of using 4,4-dimethylpent-2-yne (2f),
the reaction was regioselective, rendering only the corresponding
2-methyl-3-tert-butylcyclopentenone 8d with good yield (entry
10). However, only in this case both diastereomeric cis/trans isomer
were detected and isolated. The assignation of relative configura-
tion was performed in basis of the constant coupling between both
hydrogen of cyclopentenone ring. The minor isomer showed
a J¼2.8 Hz, and it was assumed that it was the cis-8d. Meanwhile
the major isomer showed a J¼1.0 Hz, and it was assumed that it was
the trans-8d0. These constant coupling for all compounds 8 were
always higher than 2.5 Hz and they were assigned as cis-ones. The
reaction using a para-substituted cinnamoyl chloride gave the ex-
pected product 8 with similar results to previous trials, in-
dependently of the electron-nature of the group (entries 11 and 12).
Entry
Ar
R
No.
4a (%)b
1
2
3
Ph
Ph
4-MeC6H4
Me
nBu
Me
10a
10b
10c
91
87
79
a
Reaction carried out using 1j (1.5 mmol) and 9 (1.0 mmol) in toluene (2.5 mL)
under an argon atmosphere.
b
Isolated yield after column chromatography.
Then, we tried to extend the scope of the reaction to simple
alkynes of type 2, in which the postulated cationic intermediate is
less stable. The reaction between the acid chloride 1j and hex-3-
yne (2b) did not produce the expected cyclopenta[a]naphthlen-1-
ones of type 10, but yielded the product 11a (Table 6, entry 1)

R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
7059
intermediate, which, then cyclized to yield compound 12.
This behavior was previously described for other Lewis acid
catalysts.3c,14
The hypothetic mechanism pathway is depicted in Scheme 3.
The adsorption of acyl chloride on the surface of the magnetite with
a debilitation of the corresponding chlorine carbon bond in A is the
first step of the process. The addition to the alkyne reagent would
generate the key vinyl cation C. This intermediate C renders dif-
ferent intermediates depending on the nature of the substituent R1
of the starting acyl chloride. So, the usual pathway was the reaction
with chloride in a syn-manner (D). However, if the R1 group has
a carbonecarbon double bond (R1¼ArCH]CH) the vinyl cation C
suffers a cyclization process to give intermediate E, or if the R1
group has the possibility of suffering electrophilic aromatic sub-
stitution (R1¼1-naphthyl) the intermediate yielded cation F.
Fig. 1. ORTEP drawing of compound 10a.
Table 6
Preparation of (E)-3-alkylidene-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-onesa
Entry
R
No.
Yield (%)b
1
2
3
Me
nPr
nBu
11a
11b
11c
85
87c,d
84
a
Reaction carried out using 1j (1.5 mmol) and 2 (1.0 mmol) in toluene (2.5 mL)
under an argon atmosphere.
b
Isolated yield after column chromatography.
Reaction performed during 4 h.
A 5% of chlorovinyl ketone of type 3m was isolated.
c
d
with a good chemical yield. To the best of our knowledge, this type
of compound has been synthesized for the first time, and its for-
mation could be explained by a simple isomerization, in the re-
action media, from the a,b-unsaturated ketone of type 10 to the
corresponding conjugated stryryl unit 11. We do not have any clear
explanation of the driving force for this process. The structure of
compound 11 was unambiguously assigned according to NOESY,
HSQC- and HMBC-NMR experiments, as well as X-ray data for
compound 11a (see Fig. 2). The reaction seems to be general,
obtaining similar results for all tested aliphatic-substituted internal
alkynes (entries 2 and 3).
Scheme 3. Proposed mechanism for the addition of acid chloride to alkynes and fur-
ther evolution.
2.3. Furan cyclization
Very recently, the Tsuji research group has found a new entry to
the direct synthesis of 2,5-disubstituted furans starting from acid
chlorides and terminal alkynes, in moderate yields for phenyl de-
rivatives and low yields for thienyl ones.8a The possible catalytic
pathway involved the dehydrochlorination of the corresponding
chlorovinyl ketone followed by cyclization of formed allenic ketone.
Since zinc chloride, in combination with an amine, has been in-
troduced as a catalyst for this elimination process,15 we studied the
activity of other Lewis acid catalysts for this tandem dehydro-
chlorinationecyclization process (Table 7), with the idea in mind to
integrate all processes starting from internal alkynes to yield 1,2,5-
trisubstituted furans.
Fig. 2. ORTEP drawing of compound 11a.
To avoid the formation of an exo-cyclic double bond in com-
pounds 11, we repeated the reaction with alkyne 2f (Scheme 2).
However, in this case, a 1,2-shift methyl migration took place, after
the vinyl cation formation to give the more stable allylic
The reaction of chlorovinyl ketone 3a with nano-power mag-
netite did not yield the expected furan 13a after 7 days at 130 ꢀC.
However, the same process but using rhodium trichloride gave the
product 13a in a moderate yield. Then other transition salts were
tested, with palladium and iridium giving excellent results (entries
3 and 4). Finally, the same process was conducted with the related
transition metal oxides impregnated on magnetite (entries 5e7).
From the comparison of the results from both types of catalysts
Scheme 2. Preparation of compound 12.

7060
R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
Table 7
Cyclization of
Table 8
b
-chlorovinyl ketone 3aa
One-pot synthesis of 1-aryl-2,4-dialkylfuransa
Entry
Catalyst (mol %)
Yield 13a (%)b
c
1
2
3
4
5
6
7
Fe3O4 (65)
0
54
89
87
75
82
95
Entry
Ar
R
No.
Yield (%)b
RhCl3 (10)
PdCl2 (10)
IrCl3 (10)
Rh2O3eFe3O4 (0.8)
PdOeFe3O4 (1.4)
IrO2eFe3O4 (0.07)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
nPr
nPr
nPr
nPr
nPr
Me
nPr
nPr
nPr
13a
13a
13a
13a
13a
13b
13c
13d
13e
62c,d
87c,e
90c,f
70g
88 (51)
91 (68)
76 (55)
94 (69)
74 (41)
a
4-ClC6H4
4-MeOC6H4
2-Thienyl
Reaction carried out using 3a (1 mmol) in toluene (2.5 mL) under an argon
atmosphere.
b
c
Isolated yield after column chromatography.
Powder<5 m.
m
a
Reaction carried out using 1 (1.5 mmol) and 2 (1.0 mmol) in toluene (2.5 mL)
under an argon atmosphere.
Isolated yield after column chromatography; In the parenthesis appear the re-
sults using Rh2O3eFe3O4 (0.8 mol %) as catalyst for the step ii.
could be concluded that the heterogeneous catalysts gave better
results than homogenous ones, since with amounts around 1 mol %
of heterogeneous catalysts it was possible to obtain similar results
to the reached using homogenous ones at 10 mol % loading.
Once we found that the dehydrochlorinationecyclization pro-
cess was catalyzed by different metallic oxides impregnated on
magnetite (Table 7) and that the magnetite could catalyze the ad-
dition of acid chlorides to internal alkynes, we tried to perform the
whole integrated process. The reaction of chloride 1a with the al-
kyne 2a gave the expected product 13a after seven days at 130 ꢀC.
However, the chemical yield was moderate, independently of the
catalyst used (Scheme 4). Then, we carried out the reaction with
IrO2eFe3O4 at 70 ꢀC during 1 h (chloroacylation process) and, after
that, the temperature was increased up to 130 ꢀC, with the yield of
compound 13a and 3a being 59 and 30%, respectively.
b
c
Reaction performed during 7 d.
In the step ii, only RhCl3 (1 mol %) was used as catalyst.
In the step ii, only PdCl2 (1 mol %) was used as catalyst.
In the step ii, only IrCl3 (1 mol %) was used as catalyst.
d
e
f
g
In the step ii, only PdOeFe3O4 (1.2 mol %) was used as catalyst.
(entry 6). Even, quite similar results were obtained independently
of the presence of electron-withdrawing or -donating groups in the
ring of acyl chloride (entries 7 and 8). Finally, it should be pointed
out that the protocol rendered similar result in the special case of
the thienyl derivative (entry 9), which was a challenging example
for the construction of more simple 2,5-disubstituted furans.8a
3. Conclusion
In conclusion, we have demonstrated that simple and com-
mercially available magnetite is a good catalyst for the chlor-
oacylation of internal alkynes, as well as terminal ones, yielding the
corresponding chlorovinyl ketones with good yields. The process
could be applied to the synthesis of 5-chloro-4-arylcyclopent-2-
enones, 3-aryl-1H-cyclopenta[a]naphthalen-1-ones, and (E)-3-
alkylidene-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-ones, just
by changing either the starting acyl chloride or alkyne. The ac-
ceptable to excellent regio- and stereo-selectivity of the process,
together with the low price of catalyst and the simplicity of the
process could anticipate a good future for the process shown in this
study not only in the laboratory but also in industry. Moreover, the
use of iridium impregnated on magnetite into an integrated process
allowed us the one-pot synthesis of 1-aryl-2,4-dialkylfurans with
good yields, independently of the nature of the starting regents,
including heteroaromatic ones, with the low catalyst loading being
an important issue.
Scheme 4. Direct Synthesis of Furan 13a.
We believed that the main reason for this behavior was that the
excess of acid chloride decomposed the catalyst, and formed the
corresponding less active and soluble transition metal chloride. To
prove this hypothesis we perform a two-step one-pot process
(Table 8). After carrying out the standard reaction of chloride 1a
with alkyne 2a catalyzed by nano-powder magnetite, this catalyst
was removed by a magnet and RhCl3 (1 mol %, entry 1), PdCl2
(1 mol %, entry 2), or IrCl3 (1 mol %, entry 3) was added to this
mixture giving in all cases better results than the strategy showed
in Scheme 3. Instead of homogenous salt, we, then, studied the
same process but using the impregnated catalyst. After removing
the magnetite by the magnet, the corresponding palladium im-
pregnated on magnetite catalyst was added (1.2 mol %, entry 4)
obtaining a similar result to the obtained one using the homoge-
nous catalyst. The protocol using iridium impregnated catalyst
(0.07 mol %) gave an excellent result (entry 5, 88%), since the same
reaction but using IrCl3 (0.07 mol %) yielded 43% of compound 13a.
Then, the scope of the reaction using IrO2eFe3O4 was tested finding
that the length of the alkyne side chain did not influence the result
4. Experimental section
4.1. General information
XPS analyses were carried out on a VG-Microtech Multilab. TEM
images were obtained on a JEOL, model JEM-2010 equipped with an
X-ray detector OXFORD INCA Energy TEM 100 for microanalysis
(EDS). XRF analyses were obtained on a PHILIPS MAGIX PRO
(PW2400) X-ray spectrometer equipped with a rhodium X-ray tube
and a beryllium window. BET isotherms were carried out on
a AUTOSORB-6 (Quantachrome), using N2. Melting points were
obtained with a Reichert Thermovar apparatus. NMR spectra were
recorded on a Bruker AC-300 (300 MHz for 1H and 75 MHz for 13C)

R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
7061
using CDCl3 as a solvent and TMS as internal standard for 1H and
13C; chemical shifts are given in
(parts per million) and coupling
29.7, 32.3, 36.9, 128.7 (2C), 129.4 (2C), 133.6, 136.4, 137, 137.1, 197.5;
EIMS m/z: 278 (Mþ, 10%), 243 (25), 237 (10), 235 (28), 187 (10), 179
(23), 145 (11), 105 (100), 77 (46). HRMS calcd for C17H23ClO:
278.1437; found: 278.1434.
d
constants (J) in Hertz. FT-IR spectra were obtained on a JASCO
4100LE (Pike Miracle ATR) spectrophotometer. Mass spectra (EI)
were obtained at 70 eV on a Himazdu QP-5000 spectrometer, giv-
ing fragment ions in m/z with relative intensities (%) in parentheses.
HRMS spectra were obtained with a Finnigan High-resolution Mass
Spectrometer (MAT95S model). Single-Crystal XRD analyses were
obtained on a Bruker CCD-Apex equipped with an X-ray tube with
Mo anode. Crystallographic data for compounds 10a (CCDC 910476)
and 11a (CCDC 910475) can be obtained free of charge from Cam-
bridge Crystallographic Data Centre. Thin layer chromatography
(TLC) was carried out on Schleicher & Schuell F1400/LS 254 plates
coated with a 0.2 mm layer of silica gel; detection by UV254 light,
staining with phosphomolybdic acid [25 g phosphomolybdic acid,
10 g Ce(SO4)2 4H2O, 60 mL of concentrated H2SO4, and 940 mL
H2O]. Column chromatography was performed using silica gel 60 of
35e70 mesh. All reagents were commercially available (Acros,
Aldrich, Fluorochem) and were used as received.
4.3.2. (Z)-3-Chloro-2-ethyl-1-phenylpent-2-en-1-one (3b).10 Yellow
oil, Rf¼0.7 (hexane/ethyl acetate 4:1); tR 12.4; IR (cmꢂ1): 1666,
1638, 1596, 1449, 1285, 1242, 822, 711, 689; 1H NMR (300 MHz,
CDCl3):
d
1.03 (t, J¼7.6 Hz, 3H, ClCCCH2CH3), 1.04 (t, J¼7.3 Hz, 3H,
ClCCH2CH3), 2.2 (q, J¼7.3 Hz, 2H, ClCCH2), 2.53 (q, J¼7.6 Hz, 2H,
ClCCCH2), 7.45e7.5 (m, 2H, OCCCHCH ꢁ2), 7.55e7.65 (m, 1H,
OCCCHCHCH), 7.85e7.95 (m, 2H, OCCCH ꢁ2); 13C NMR (75 MHz,
CDCl3):
d 11.8, 12.3, 25.7, 30.6, 128.7 (2C), 129.3 (2C), 133.6, 136.4,
137.3, 137.4, 197.3; EIMS m/z: 222 (Mþ, 10%), 187 (59), 159 (32), 158
(13), 105 (100), 77 (67).
4.3.3. (Z)-3-Chloro-2-pentyl-1-phenyloct-2-en-1-one (3c). Yellow
oil; Rf¼0.73 (hexane/ethyl acetate 4:1); tR 15.5; IR (cmꢂ1): 1669,
1596, 1465, 1448, 1314, 1259, 719, 689; 1H NMR (300 MHz, CDCl3):
d
0.79, 0.84 (2t, J¼7.1 and 7 Hz, respectively, 3H each one, CH3 ꢁ2),
4.2. General procedure for the preparation of catalysts
1.05e1.2, 1.2e1.35, 1.35e1.6 (3m, 4H each one, CH2 ꢁ6), 2.18 (t,
J¼7.3 Hz, 2H, ClCCH2), 2.49 (t, J¼7.6 Hz, 2H, ClCCCH2), 7.4e7.5 (m,
2H, OCCCHCH ꢁ2), 7.55e7.65 (m, 1H, OCCCHCHCH), 7.85e7.95 (m,
To a stirred solution of the corresponding metal salt MClx
(1 mmol) in deionized water (150 mL) was added commercial
2H, OCCCH ꢁ2); 13C NMR (75 MHz, CDCl3):
d 13.8, 13.9, 22.2, 22.3,
available Fe3O4 (4 g, 17 mmol, powder <5
m
m, BET area: 9.86 m2/g).
27.1, 27.3, 30.8, 31.5, 32.6, 37.1, 128.7 (2C), 129.4 (2C), 133.6, 136.4,
137, 137.1, 197.4; EIMS m/z: 270 (7%), 227 (14), 105 (100), 77 (34).
HRMS calcd for C19H27ClOeHCl: 270.1984; found: 270.1995.
After 10 min at room temperature, the mixture was slowly basified
with NaOH (1 M) until pH around 13. The mixture was stirred
during one day at room temperature in air. After that, the catalyst
was filtered and washed several times with deionized water
(3ꢁ10 mL). The solid was dried at 100 ꢀC during 24 h in a standard
glassware oven obtaining the expected catalyst. The rhodium cat-
alyst gave an incorporation of rhodium of 1.7% according to XRF; by
XPS the rhodium on the surface was determined as 17.5%; the BET
area surface was 8.4 m2/g. The silver catalyst gave an incorporation
of silver of 2.7% according to XRF; by XPS the silver on the surface
was determined as 6.2%; the BET area surface was 7.4 m2/g. The
tungsten catalyst gave an incorporation of tungsten of 2.1%
according to XRF; by XPS the tungsten on the surface was de-
termined as 13.6%; the BET area surface was 7.7 m2/g. The gold
catalyst gave an incorporation of gold of 1.5% according to XRF; by
XPS the gold on the surface was determined as 14.8%; the BET area
surface was 7.9 m2/g.
4.3.4. (Z)-3-Chloro-1,3-diphenylprop-2-en-1-one (3d).10 Pale yellow
oil; Rf¼0.37 (hexane/ethyl acetate 4:1); tR 16.3; IR (cmꢂ1): 1662,
1597, 1574, 1446, 1234, 1206, 1016, 756, 687; 1H NMR (300 MHz,
CDCl3):
d 7.35 (s, 1H, ClCCH), 7.4e7.5, 7.55e7.6, 7.7e7.8, 7.95e8.05
(4m, 5, 1, 2 and 2H, respectively, Ph ꢁ2); 13C NMR (75 MHz, CDCl3):
d
121.4, 127.1 (2C), 128.6 (2C), 128.6 (2C), 128.7 (2C), 130.5, 133.3,
137.3, 137.7, 143.3, 189.8; EIMS m/z: 244 (Mþþ2, 15%), 243 (Mþþ1,
39), 242 (Mþ, 46), 241 (100), 179 (18), 178 (19), 167 (10), 165 (31),
105 (61), 102 (58), 101 (17), 89 (16), 77 (96).
4.3.5. (Z)-2-Butyl-3-chloro-1-(4-chlorophenyl)hept-2-en-1-one
(3e). Yellow oil; Rf¼0.73 (hexane/ethyl acetate 4:1); tR 15.6; IR
(cmꢂ1): 1670, 1586, 1465, 1399, 1266, 1211, 1091, 1013, 932, 846, 771,
757; 1H NMR (300 MHz, CDCl3):
d
0.8, 0.88 (2t, J¼7.3 and 7.1 Hz,
respectively, 3H each one, CH3 ꢁ2), 1.1e1.25, 1.3e1.45, 1.45e1.55
(3m, 2, 4 and 2H, respectively, CH2 ꢁ4), 2.19 (t, J¼7.4 Hz, 2H,
ClCCH2), 2.5 (t, J¼7.2 Hz, 2H, ClCCCH2), 7.48 (d, J¼8.5 Hz, 2H, ClCCH
ꢁ2), 7.86 (d, J¼8.5 Hz, 2H, ClCCHCH ꢁ2),; 13C NMR (75 MHz, CDCl3):
4.3. General procedure for the addition reactions
To a stirred solution of alkyne (2 or 9, 1 mmol) in dry toluene
(2.5 mL) under argon atmosphere were added Fe3O4 (25 mg or 10 mg)
and the corresponding acid derivative (1, 5 or 7, 1.5 mmol). The
resulting mixture was stirred at 70 ꢀC during one hour. The catalyst
was removed by a magnet and the resulting mixture was quenched
with water (5 mL) and extracted with EtOAc (3ꢁ5 mL). The organic
phases were dried over MgSO4, followed by evaporation under re-
duced pressure to remove the solvent. The product was usually pu-
rified by chromatography on silica gel (hexane/ethyl acetate) to give
the corresponding products 3, 4, 6, 8, 10, 11, and 12. Physical and
spectroscopicdata, aswell as literature forknown compounds, follow:
d
13.7, 13.7, 21.7, 22.5, 29.6, 29.7, 32.3, 37, 129.2 (2C), 130.8 (2C),
134.7, 136.7, 137.3, 140.2, 196.2; EIMS m/z: 277 (11%), 141 (34), 140
(9), 139 (100), 111 (27). HRMS calcd for C17H22Cl2OeCl: 277.1359;
found: 277.1340.
4.3.6. (Z)-2-Butyl-1-(4-[tert-butyl]phenyl)-3-chlorohept-2-en-1-one
(3f). Yellow oil; Rf¼0.77 (hexane/ethyl acetate 4:1); tR 16.4; IR
(cmꢂ1): 1667, 1603, 1463, 1268, 1188, 1107, 933, 852, 780, 719; 1H
NMR (300 MHz, CDCl3):
d
0.77, 0.87 (2t, J¼7.3 and 7.1 Hz, re-
spectively, 3H each one, CH3 ꢁ2), 1.1e1.2, 1.25e1.45, 1.45e1.6 (3m
with s at 1.36, 9, 2, 4 and 2H, respectively, CH2 ꢁ4 and C(CH3)3), 2.19
(t, J¼7.3 Hz, 2H, ClCCH2), 2.51 (t, J¼7.1 Hz, 2H, ClCCCH2), 7.5 (d,
J¼8.5 Hz, 2H, OCCCHCH ꢁ2), 7.84 (d, J¼8.5 Hz, 2H, OCCCH ꢁ2); 13C
4.3.1. (Z)-2-Butyl-3-chloro-1-phenylhept-2-en-1-one (3a). Brown
oil; Rf¼0.77 (hexane/ethyl acetate 4:1); tR 14.3; IR (cmꢂ1): 1668,
1637, 1596, 1579, 1465, 1448, 1313, 1268, 1212, 935, 719, 689; 1H
NMR (75 MHz, CDCl3):
d 13.6, 13.7, 21.7, 22.5, 29.6, 29.7, 31 (3C),
NMR (300 MHz, CDCl3):
d
0.77 (t, J¼7.3 Hz, 3H, ClCCH2CH2CH2CH3),
32.3, 35.2, 36.9, 125.7 (2C), 129.4 (2C), 133.8, 136.4, 137.2, 157.5,
197.1; EIMS m/z: 298 (12%), 283 (11), 269 (12), 162 (12), 161 (100).
HRMS calcd for C21H31ClOeHCl: 298.2297; found: 298.2312.
0.86 (t, J¼7.1 Hz, 3H, ClCCCH2CH2CH2CH3), 1.1e1.2, 1.25e1.45,
1.45e1.55 (3m, 2, 4 and 2H, respectively, CH2 ꢁ4), 2.18 (t, J¼7.3 Hz,
2H, ClCCH2), 2.5 (t, J¼7.1 Hz, 2H, ClCCCH2), 7.4e7.5 (m, 2H,
OCCCHCH ꢁ2), 7.55e7.65 (m, 1H, OCCCHCHCH), 7.85e7.95 (m, 2H,
4.3.7. (Z)-2-Butyl-3-chloro-1-(4-methoxyphenyl)hept-2-en-1-one
(3g). Yellow oil; Rf¼0.43 (hexane/ethyl acetate 4:1); tR 16.2; IR
OCCCH ꢁ2); 13C NMR (75 MHz, CDCl3):
d
13.7, 13.7, 21.7, 22.5, 29.6,

7062
R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
(cmꢂ1): 1659, 1597, 1255, 1215, 1159, 1030, 845; 1H NMR (300 MHz,
CDCl3):
(10), 239 (29). HRMS calcd for C22H17ClO2eHCl: 312.1150; found:
312.1113.
d
0.73, 0.82 (2t, J¼7.3 and 7.1 Hz, respectively, 3H each one,
CH3 ꢁ2), 1.05e1.2, 1.2e1.35, 1.35e1.5 (3m, 2, 4 and 2H, respectively,
CH2 ꢁ4), 2.15 (t, J¼7.4 Hz, 2H, ClCCH2), 2.45 (t, J¼7.1 Hz, 2H,
ClCCCH2), 3.84 (s, 3H, OCH3), 6.92 (d, J¼8.8 Hz, 2H, OCCCHCH ꢁ2),
4.3.12. (Z)-4-Butyl-5-chloro-1-phenylnon-4-en-3-one and (E)-4-
butyl-5-chloro-1-phenylnon-4-en-3-one [(Z)-3l/(E)-4l: 3/1]. Brown
oil; Rf¼0.73 (hexane/ethyl acetate 4:1); tR 15.6; IR (cmꢂ1): 1697,
7.84 (d, J¼8.8 Hz, 2H, OCCCH ꢁ2); 13C NMR (75 MHz, CDCl3):
d 13.6,
13.6, 21.6, 22.4, 29.5, 29.6, 32.3, 36.8, 55.3, 113.9 (2C), 129.2, 131.7
(2C),135.7, 137,163.9, 195.8; EIMS m/z: 272 (9%), 243 (10), 135 (100),
77 (10). HRMS calcd for C18H25ClO2eHCl: 272.1776; found:
272.1780.
1603, 1496, 1454, 747, 698; 1H NMR (300 MHz, CDCl3):
d 0.85e1 (m,
8H, CH3 ꢁ4), 1.2e1.6 (m, 11H, CH2 ꢁ8), 2.15e2.45 (m, 5H, CH2 ꢁ4),
2.85e3 (m, 5H, CH2 ꢁ4), 7.2e7.35 (m, 7H, Ph ꢁ2); 13C NMR
(75 MHz, CDCl3):
d 13.7, 13.8, 13.9, 13.9, 21.9, 22, 22.4, 22.5, 29.5,
29.7, 29.8, 29.8, 29.9, 30.2, 30.6, 30.9, 34.6, 36.6, 43.9, 44.6, 126,
126.2, 128.3 (2C), 128.4 (2C), 128.4 (2C), 128.5 (2C), 132, 138.8, 139.2,
140.1, 140.8, 141.1, 204.2 (C]O, Z), 206.2 (C]O, E); EIMS m/z: 270
(19%), 241 (42), 180 (13), 179 (100), 166 (12), 137 (39), 105 (66), 91
(63). HRMS calcd for C19H27ClOeHCl: 270.1984; found: 270.1973.
4.3.8. (Z)-2-Butyl-3-chloro-1-(2-methoxyphenyl)hept-2-en-1-one
(3h). Pale yellow oil; Rf¼0.47 (hexane/ethyl acetate 4:1); tR 15.1; IR
(cmꢂ1): 1656, 1597, 1484, 1463, 1435, 1288, 1246, 1162, 1024, 931,
754; 1H NMR (300 MHz, CDCl3):
d
0.81, 0.86 (2t, J¼7.3 and 7.2 Hz,
respectively, 3H each one, CH3 ꢁ2), 1.15e1.25, 1.25e1.35, 1.35e1.45,
1.45e1.55 (4m, 2H each one, CH2 ꢁ4), 2.35 (t, J¼7.5 Hz, 2H, ClCCH2),
2.46 (t, J¼7.5 Hz, 2H, ClCCCH2), 3.86 (s, 3H, OCH3), 6.96 (d, J¼8.3 Hz,
1H, CH3OCCH), 7.02 (td, J¼7.6 Hz, 4J¼0.7 Hz,1H, CH3OCCCHCH), 7.49
(td, J¼8.2, Hz, 4J¼1.7 Hz, 1H, CH3OCCHCH), 7.62 (dd, J¼7.6 Hz,
4.3.13. (Z)-2-Butyl-3-chloro-1-(naphthalen-1-yl) hept-2-en-1-one
(3m). Orange oil; Rf¼0.73 (hexane/ethyl acetate 4:1); tR 18.8; IR
(cmꢂ1): 1699, 1582, 1519, 1458, 1259, 1069, 1019, 822, 797; 1H NMR
(300 MHz, CDCl3):
d
0.96, 1.01 (2t, J¼7.2 and 7.3 Hz, respectively, 3H
4J¼1.7 Hz, 1H, CH3OCCCH); 13C NMR (75 MHz, CDCl3):
d
13.7, 13.8,
each one, CH3 ꢁ2), 1.35e1.45, 1.45e1.55, 1.6e1.7 (3m, 2, 4 and 2H,
respectively, CH2 ꢁ4), 2.28, 2.59 (2t, J¼7.2 and 7.5 Hz, respectively,
2H each one, CCH2 ꢁ2), 7.25e7.35, 7.45e7.5, 7.7e7.75, 7.85e7.9,
8.65e8.7 (5m, 3, 1, 1, 1 and 1H, respectively, ArH ꢁ7); 13C NMR
21.9, 22.5, 29.7, 29.9, 31.8, 36.6, 55.6, 111.7, 120.5, 127.9, 131.1, 133.8,
139.5, 139.8, 158.6, 196.5; EIMS m/z: 308 (Mþ, 0.1%), 135 (100), 77
(12). HRMS calcd for C18H25ClO2: 308.1543; found: 308.1515.
(75 MHz, CDCl3): d 13.9, 14, 22.6, 22.8, 23, 25.9, 30, 31.7, 117.7, 122.8,
4.3.9. (Z)-2-Butyl-3-chloro-1-(4-fluoronaphthalen-1-yl)hept-2-en-
1-one (3i). Orange oil; Rf¼0.77 (hexane/ethyl acetate 4:1); tR 18.3;
IR (cmꢂ1): 1661, 1627, 1599, 1463, 1424, 1243, 1214, 1050, 769; 1H
123.5, 125.3, 128.2, 128.8 (2C), 133.4, 133.9, 134, 147, 155.6, 200.8;
EIMS m/z: 293 (MþꢂCl, 22%), 292 (94), 250 (39), 249 (100), 236
(20), 235 (19), 221 (11), 208 (23), 207 (79), 202 (11), 195 (18), 194
(52),193 (85),191 (19),190 (10),189 (19),179 (49),178 (62),177 (11),
176 (15), 165 (41), 152 (16). HRMS calcd for C21H25ClOeHCl:
292.1827; found: 292.1834.
NMR (300 MHz, CDCl3):
d
0.76, 0.89 (2t, J¼7.3 and 7.2 Hz, re-
spectively, 3H each one, CH3 ꢁ2), 1.1e1.25, 1.3e1.4, 1.45e1.6 (3m, 2,
2 and 4H, respectively, CH2 ꢁ4), 2.30 (t, J¼7.4 Hz, 2H, ClCCH2), 2.58
3
(t, J¼7.6 Hz, 2H, ClCCCH2), 7.19 (dd, J(H,F)¼9.6 Hz, J¼8.3 Hz, 1H,
FCCH), 7.6e7.7 (m, 1H, FCCCHCH), 7.73 (ddd, J¼8.6 and 6.8 Hz,
4.3.14. (E)-2-Butyl-3-chloro-1-phenylhept-2-en-1-one
(4a). Pale
4J¼1.1 Hz, 1H, FCCCHCHCH), 7.9 (dd, J¼8.3 Hz, J(H,F)¼, 5.6 Hz,
yellow oil; Rf¼0.73 (hexane/ethyl acetate 4:1); tR 14.6; IR (cmꢂ1):
4
FCCHCH), 8.2 (d, J¼8.3 Hz, 1H, FCCCH), 8.96 (d, J¼8.6 Hz, 1H,
1668, 1636, 1596, 1579, 1465, 1448, 1268, 1213, 935, 720, 690; 1H
FCCCCH); 13C NMR (75 MHz, CDCl3):
d
13.6, 13.8, 21.8, 22.5, 29.9
NMR (300 MHz, CDCl3):
d
0.89, 0.99 (2t, J¼7.6 and 7.3 Hz, re-
(2C), 32.6, 37, 108.2 (d, 2J(C,F)¼21 Hz), 120.9 (d, 3J(C,F)¼6.4 Hz), 124.2
spectively, 3H each one, CH3 ꢁ2), 1.3e1.55, 1.6e1.7 (2m, 6 and 2H,
respectively, CH2 ꢁ4), 2.35e2.4, 2.45e2.5 (2m, 2H each one, CCH2
ꢁ2), 7.45e7.5 (m, 2H, OCCCHCH ꢁ2), 7.55e7.65 (m, 1H,
OCCCHCHCH), 7.85e7.95 (m, 2H, OCCCH ꢁ2); 13C NMR (75 MHz,
2
4
4
(d, J(C,F)¼15.7 Hz), 125.8 (d, J(C,F)¼2 Hz), 127 (d, J(C,F)¼1.6 Hz),
4
3
129.5, 130.3 (d, J(C,F)¼4.2 Hz), 132.3 (d, J(C,F)¼10.1 Hz), 132.7 (d,
3J(C,F)¼5.6 Hz),138.9,139.8,161.7 (d, 1J(C,F)¼261.5 Hz),197.9; EIMS m/
z: 346 (Mþ, 0.4%), 311 (22), 310 (100), 268 (40), 267 (90), 255 (11),
254 (32), 253 (18), 239 (13), 226 (31), 225 (80), 213 (14), 212 (47),
211 (67), 209 (16), 207 (22), 197 (36), 196 (47), 183 (32), 170 (11).
HRMS calcd for C21H24ClFO: 346.1500; found: 346.1474.
CDCl3): d 13.7, 13.9, 22.2, 22.6, 29.6, 30.5, 31.4, 34.5, 128.7 (2C), 129.4
(2C), 133.4, 135.7, 136.6, 137, 197.3; EIMS m/z: 280 (Mþþ2, 11%), 279
(Mþþ1, 10), 278 (Mþ, 33), 277 (11), 243 (32), 235 (17), 201 (11), 199
(12), 187 (11), 179 (18), 145 (14), 105 (100), 77 (50). HRMS calcd for
C17H23ClO: 278.1437; found: 278.1428.
4.3.10. (Z)-2-Butyl-3-chloro-1-(thiophen-2-yl)hept-2-en-1-one
(3j). Pale yellow oil; Rf¼0.67 (hexane/ethyl acetate 4:1); tR 14.9; IR
(cmꢂ1): 1644, 1514, 1409, 1274, 1049, 722; 1H NMR (300 MHz,
4.3.15. (Z)-3-Bromo-2-butyl-1-phenylhept-2-en-1-one (6). Brown
oil; Rf¼0.77 (hexane/ethyl acetate 4:1); tR 14.3; IR (cmꢂ1): 1668,
1631, 1596, 1580, 1463, 1449, 1313, 1264, 1211, 934, 716, 688; 1H
CDCl3):
d
0.79, 0.88 (2t, J¼7.3 and 7.2 Hz, respectively, 3H each one,
CH3 ꢁ2), 1.15e1.25, 1.3e1.4, 1.4e1.45, 1.45e1.55 (4m, 2H each one,
CH2 ꢁ4), 2.26 (t, J¼7.2 Hz, 2H, ClCCH2), 2.52 (t, J¼7.4 Hz, 2H,
ClCCCH2), 7.15 (dd, J¼4.9 and 3.8 Hz, 1H, SCHCH), 7.63 (dd, J¼3.8 Hz,
4J¼1.1 Hz, 1H, SCCH), 7.72 (dd, J¼4.9 Hz, 4J¼1.1 Hz, 1H, SCH); 13C
NMR (300 MHz, CDCl3):
d
0.68, 0.78 (2t, J¼7.3 and 7.1 Hz, re-
spectively, 3H each one, CH3 ꢁ2), 1.1e1.15, 1.15e1.35, 1.35e1.5 (3m,
2, 4 and 2H, respectively, CH2 ꢁ4), 2.20 (t, J¼7.3 Hz, 2H, ClCCH2),
2.41 (t, J¼7.2 Hz, 2H, ClCCCH2), 7.35e7.45 (m, 2H, OCCCHCH ꢁ2),
7.45e7.55 (m, 1H, OCCCHCHCH), 7.8e7.85 (m, 2H, OCCCH ꢁ2); 13C
NMR (75 MHz, CDCl3):
d 13.7, 13.8, 21.7, 22.5, 29.7, 29.8, 32.4, 37.1,
128.3, 134.3, 135.2, 137, 137.1, 144, 189.7; EIMS m/z: 284 (Mþ, 9%),
253 (19), 251 (57), 241 (12), 111 (100). HRMS calcd for C15H21ClOS:
284.1002; found: 284.1028.
NMR (75 MHz, CDCl3): d 13.6, 13.7, 21.6, 22.4, 29.4, 30.6, 35.3, 38.9,
128.7 (2C), 129.4 (2C), 130.4, 133.7, 136, 139.8, 197.1; EIMS m/z: 243
(1%), 242 (5), 213 (12), 105 (100), 77 (29). HRMS calcd for
C17H23BrO: 322.0932; found: 322.0910.
4.3.11. (Z)-3-Chloro-1-(4-methoxyphenyl)-2,3-diphenylprop-en-1-
one (3k). Orange oil; Rf¼0.33 (hexane/ethyl acetate 4:1); tR 22.5; IR
(cmꢂ1): 1604, 1509, 1346, 1249, 1175, 1028, 753, 696; 1H NMR
4.3.16. cis-2,3-Dibutyl-5-chloro-4-phenylcyclopent-2-enone (8a).
Yellow oil; Rf¼0.63 (hexane/ethyl acetate 4:1); tR 16.5; IR (cmꢂ1):
1714, 1632, 1603, 1496, 1455, 1346, 751, 700; 1H NMR (300 MHz,
(300 MHz, CDCl3):
d
3.83 (s, 3H, OCH3), 6.92 (d, J¼8.9 Hz, 2H, OCCH
ꢁ2), 7.15e7.4 (m, 12H, Ph ꢁ2 and OCCHCH ꢁ2); 13C NMR (75 MHz,
CDCl3):
d
0.76 (t, J¼7.1 Hz, 3H, OCCCH2CH2CH2CH3), 0.86 (t,
CDCl3):
d
55.2, 114.1 (2C), 121.2, 122.7, 127.5 (2C), 128 (2C), 129.8
J¼7.2 Hz, 3H, OCCCCH2CH2CH2CH3), 1.1e1.45 (m, 8H, CH2 ꢁ4), 1.9
(ddd, 2J¼14 Hz, J¼8.7 and 5.3 Hz, 1H, OCCCCH2), 2.15e2.3 (m, 2H,
OCCCH2), 2.41 (ddd, 2J¼14 Hz, J¼9.4 and 6.2 Hz, 1H, OCCCCH2), 3.90
(2C), 130.2 (2C), 131, 131.1, 131.6, 133.2 (2C), 145.1, 155.1, 160.4, 196.4;
EIMS m/z: 313 (25%), 312 (100), 311 (24), 281 (22), 268 (11), 240

R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
7063
(d, J¼2.7 Hz, 1H, OCCHCH), 3.98 (d, J¼2.7 Hz, 1H, OCCH), 7e7.05 (m,
2H, ClCHCHCCH ꢁ2), 7.15e7.3 (m, 3H, ClCHCHCCHCH ꢁ2 and
(10), 124 (100), 123 (14), 115 (12), 109 (50), 103 (11), 91 (15), 81 (24),
77 (14). HRMS calcd for C16H19ClO: 262.1124; found: 262.1116.
ClCHCHCCHCHCH); 13C NMR (75 MHz, CDCl3):
d 13.6, 13.8, 22.5,
22.6, 23.3, 28.5, 29.1, 30.6, 57.7, 62.1, 127.5 (2C), 127.8, 129.1 (2C),
138.9, 139.9, 172.6, 201.1; EIMS m/z: 306 (Mþþ2, 18%), 305 (Mþþ1,
12), 304 (Mþ, 54), 277 (24), 276 (14), 275 (71), 270 (21), 269 (100),
247 (13), 227 (13), 185 (11), 183 (11), 155 (14), 153 (10), 141 (21), 129
(17), 128 (14), 115 (17), 103 (12), 91 (32), 77 (13). HRMS calcd for
C19H25ClO: 304.1594; found: 304.1645.
4.3.21. cis-2,3-Dibutyl-5-chloro-4-(4-fluorophenyl)cyclopent-2-
enone (8e). Yellow oil; Rf¼0.67 (hexane/ethyl acetate 4:1); tR 16.3;
IR (cmꢂ1): 1715, 1633, 1605, 1508, 1464, 1458, 1348, 1227, 1159, 1097,
823, 789, 733; 1H NMR (300 MHz, CDCl3):
d
0.85 (t, J¼7.1 Hz, 3H,
OCCCH2CH2CH2CH3), 0.94 (t, J¼7.1 Hz, 3H, OCCCCH2CH2CH2CH3),
1.2e1.5 (m, 8H, CH2 ꢁ4), 1.96 (ddd, 2J¼13.7 Hz, J¼8.6, 4.7 Hz, 1H,
OCCCCH2), 2.2e2.35 (m, 2H, OCCCH2), 2.49 (ddd, 2J¼13.7 Hz, J¼9.2
and 5.7 Hz, 1H, OCCCCH2), 3.97 (d, J¼2.8 Hz, 1H, OCCHCH), 4.01 (d,
J¼2.8 Hz, 1H, OCCH), 7e7.15 (m, 4H, ArH ꢁ4); 13C NMR (75 MHz,
4.3.17. cis-5-Chloro-2,3-diethyl-4-phenylcyclopent-2-enone (8b).
Yellow oil; Rf¼0.37 (hexane/ethyl acetate 4:1); tR 14.5; IR (cmꢂ1):
1713, 1633, 1603, 1495, 1455, 1354, 760, 728, 700; 1H NMR
CDCl3):
d 2.8, 3, 13.2, 13.3, 14.1, 20.1, 20.9, 22.6, 53.6, 59.6, 122.9 (d,
3
(300 MHz, CDCl3):
d
0.99 (t, J¼7.6 Hz, 3H, OCCCCH2CH3), 1.1 (t,
2J(C,F)¼25.3 Hz, 2C), 138.1 (d, J(C,F)¼9.6 Hz, 2C), 144.6 (d,
4J(C,F)¼3.8 Hz),151.1,177 (d, 1J(C,F)¼289.5 Hz),188.5, 222.1; EIMS m/z:
324 (Mþþ2, 16%), 323 (Mþþ1, 10), 322 (Mþ, 48), 295 (24), 294 (13),
293 (72), 288 (22), 287 (100), 265 (13), 245 (11), 203 (11), 201 (11),
159 (20), 147 (12), 146 (13), 133 (14), 109 (34), 91 (14). HRMS calcd
for C19H24ClFO: 322.1500; found: 322.1489.
J¼7.6 Hz, 3H, OCCCH2CH3), 2.02 (dq, 2J¼14.5 Hz, J¼7.6 Hz, 1H,
OCCCCH2), 2.35 (q, J¼7.6 Hz, 2H, OCCCH2), 2.53 (dq, 2J¼14.5 Hz,
J¼7.6 Hz, 1H, OCCCCH2), 4.01 (d, J¼2.7 Hz, 1H, OCCHCH), 4.08 (d,
J¼2.7 Hz, 1H, OCCH), 7.1e7.15 (m, 2H, ClCHCHCCH ꢁ2), 7.3e7.4 (m,
3H, ClCHCHCCHCH ꢁ2 and ClCHCHCCHCHCH); 13C NMR (75 MHz,
CDCl3): d 11.7, 13.1, 16.8, 21.9, 57.4, 62.2, 127.5 (2C), 127.8, 129.1 (2C),
138.7, 140.7, 173.4, 201; EIMS m/z: 250 (Mþþ2, 14%), 248 (Mþ, 42),
219 (11), 214 (16), 213 (100), 185 (16), 143 (14), 141 (12), 129 (28),
128 (15), 115 (17), 91 (16), 77 (14). HRMS calcd for C15H17ClO:
248.0968; found: 248.0930.
4.3.22. cis-2,3-Dibutyl-5-chloro-4-(4-methoxyphenyl)cyclopent-2-
enone (8f). Pale yellow oil; Rf¼0.53 (hexane/ethyl acetate 4:1); tR
18.1; IR (cmꢂ1): 1713, 1631, 1611, 1511, 1463, 1249, 1176, 1033, 820;
1H NMR (300 MHz, CDCl3):
d
0.85, 0.94 (2t, J¼7.1 Hz each one, 3H
each one, CH2CH3 ꢁ2), 1.15e1.5 (m, 8H, CH2 ꢁ4), 1.99 (ddd,
2J¼13.8 Hz, J¼8.8 and 5 Hz, 1H, OCCCCH2), 2.2e2.4 (m, 2H,
OCCCH2), 2.48 (ddd, 2J¼13.8 Hz, J¼9.3 and 6.1 Hz, 1H, OCCCCH2),
3.81 (s, 3H, OCH3), 3.93 (d, J¼2.7 Hz,1H, OCCHCH), 4.02 (d, J¼2.7 Hz,
1H, OCCH), 6.89 (d, J¼8.6 Hz, 2H, CH3OCCH ꢁ2), 7.03 (d, J¼8.6 Hz,
4.3.18. cis-5-Chloro-2,3-dipentyl-4-phenylcyclopent-2-enone (8c).
Yellow oil; Rf¼0.63 (hexane/ethyl acetate 4:1); tR 17.5; IR (cmꢂ1):
1715, 1632, 1603, 1496, 1455, 1358, 748, 728, 700; 1H NMR
(300 MHz, CDCl3):
d
0.83, 0.91 (2t, J¼6.9 Hz each one, 3H each one,
CH3 ꢁ2), 1.15e1.25, 1.25e1.4, 1.4e1.55 (3m, 4H each one, CH2 ꢁ6),
1.98 (ddd, 2J¼13.8 Hz, J¼9.2 and 5.3 Hz, 1H, OCCCCH2), 2.2e2.4 (m,
2H, OCCCH2), 2.47 (ddd, 2J¼13.8, Hz, J¼9.4 and 6.6 Hz, 1H,
OCCCCH2), 3.98 (d, J¼2.7 Hz, 1H, OCCHCH), 4.06 (d, J¼2.7 Hz, 1H,
OCCH), 7.1e7.15 (m, 2H, ClCHCHCCH ꢁ2), 7.3e7.4 (m, 3H,
ClCHCHCCHCH ꢁ2 and ClCHCHCCHCHCH); 13C NMR (75 MHz,
2H, CH3OCCHCH ꢁ2); 13C NMR (75 MHz, CDCl3):
d 13.7, 13.9, 22.6,
22.7, 23.3, 28.5, 29.2, 30.6, 55.3, 57, 62.3, 114.6 (2C), 128.6 (2C),
130.9, 139.7, 159.2, 172.9, 201.3; EIMS m/z: 336 (Mþþ2, 18%), 335
(Mþþ1, 12), 334 (Mþ, 49), 305 (19), 300 (33), 299 (100), 279 (16),
277 (47), 271 (19), 269 (14), 255 (17), 243 (11), 207 (30), 171 (11),
121 (29). HRMS calcd for C20H27ClO2: 334.1700; found: 334.1666.
CDCl3):
d 13.7, 13.9, 22.2, 22.4, 23.5, 26.6, 28.1, 28.8, 31.5, 31.7, 57.8,
62.1, 127.5 (2C), 127.8, 129.1 (2C), 138.9, 139.9, 172.6, 201.1; EIMS m/
z: 334 (Mþþ2, 18%), 333 (Mþþ1, 13), 332 (Mþ, 52), 298 (24), 297
(100), 291 (27), 290 (16), 289 (79), 263 (14), 261 (39), 241 (18), 185
(14),183 (15),165 (10),155 (17),153 (13), 141 (26),129 (18),128 (17),
115 (19), 103 (14), 91 (44), 77 (14). HRMS calcd for C21H29ClO:
332.1907; found: 332.1912.
4.3.23. 2-Methyl-3-phenyl-1H-cyclopenta[a]naphthalen-1-one
(10a). Orange solid; mp 117e120 ꢀC (hexane); Rf¼0.63 (hexane/
ethyl acetate 4:1); tR 19.7; IR (cmꢂ1): 1698, 1628, 1581, 1565, 1519,
1440, 1329, 1217, 1066, 834, 753, 701; 1H NMR (300 MHz, CDCl3):
d
1.95 (s, 3H, CH3), 7.25 (d, J¼8.1 Hz, 1H, OCCCCHCHC), 7.34 (t,
J¼8.5 Hz, 1H, OCCCCHCHCH), 7.45e7.6 (m, 6H, Ph and
OCCCCHCHCH), 7.69 (d, J¼8.3 Hz, 1H, OCCCCCHCHCH), 7.78 (d,
J¼8.1 Hz, 1H, OCCCCHCHC), 8.77 (d, J¼8.5 Hz, 1H, OCCCCHCHCH);
4.3.19. cis-3-(tert-Butyl)-5-chloro-2-methyl-4-phenylcyclopent-2-
enone (8d). Pale yellow oil; Rf¼0.73 (hexane/ethyl acetate 4:1); tR
14.7; IR (cmꢂ1): 1713, 1636, 1603, 1495, 1484, 1455, 1313, 1143, 1022,
13C NMR (75 MHz, CDCl3):
d 8.4, 118.8, 122.7, 123.5, 125.5, 127.9 (2C),
128.2, 128.6 (2C), 128.9 (2C), 129.1, 129.7, 132.6, 133.7, 133.9, 147,
152.7, 200.1; EIMS m/z: 271 (Mþþ1, 20%), 270 (Mþ, 100), 269 (41),
253 (11), 242 (22), 241 (46), 240 (17), 239 (46), 226 (13), 215 (15),
120 (17). HRMS calcd for C20H14O: 270.1045; found: 270.1037.
Crystal data: C20H14O, M¼270.31; crystal size max¼0.25, mid¼0.24,
min¼0.03; Monoclinic, space group P21/c, a¼12.7ꢀ14 (17), b¼13.994
966, 759, 700; 1H NMR (300 MHz, CDCl3):
d 1.37 (s, 9H, C(CH3)3), 2
(d, 5J¼0.7 Hz, 3H, CH3), 3.79 (dd, J¼2.8 Hz, 5J¼0.7 Hz, 1H, OCCHCH),
3.99 (d, J¼2.8 Hz, 1H, OCCH), 7.1e7.15, 7.3e7.4 (2m, 2 and 3H, re-
spectively, Ph); 13C NMR (75 MHz, CDCl3):
d 18.3, 29.5 (3C), 34, 60.6,
62.2, 127.6 (2C), 127.9, 129.2 (2C), 139.3, 145.3, 166, 200.8; EIMS m/z:
264 (Mþþ2, 16%), 262 (Mþ, 47), 247 (16), 228 (18), 227 (100), 200
(15),199 (91),185 (17),183 (12),169 (13),165 (13),157 (16),155 (12),
153 (11), 143 (15), 142 (12), 141 (19), 129 (15), 128 (21), 115 (15), 105
(18), 103 (14), 91 (26), 77 (18). HRMS calcd for C16H19ClO: 262.1124;
found: 262.1080.
3
ꢁ
ꢁ
(18), c¼8.433 (11) A,
a
¼90ꢀ,
b
¼108.49ꢀ (3),
g
¼90 ; V¼1423 (3) A ;
rcalcd¼1.262 g/cm3; 2qmax¼50.42; radiation type: Mo,
l
¼0.71073 A;
ꢁ
data collection based on three
u
-scan runs (starting
u
¼ꢂ34ꢀ) at
values
F
¼0ꢀ, 120ꢀ, 240ꢀ with the detector at 2
q
¼ꢂ32ꢀ. An addi-
tional run of 100 frames, at 2
q
¼ꢂ32ꢀ,
u
¼ꢂ34ꢀ and
F
¼0ꢀ, was ac-
quired to improve redundancy. For each of these runs, 606 frames
were collected at 0.3ꢀ intervals and 30 s per frame. T¼25ꢃ1 ꢀC,
measured and independent reflections¼2522, reflections included
4.3.20. trans-3-(tert-Butyl)-5-chloro-2-methyl-4-phenylcyclopent-2-
enone (8d0). Pale yellow oil; Rf¼0.67 (hexane/ethyl acetate 4:1); tR
14.8; IR (cmꢂ1): 1712, 1649, 1602, 1494, 1479, 1465, 1241, 703; 1H
in refinement¼10,535, I>2/
s. The diffraction frames were in-
NMR (300 MHz, CDCl3):
d
1.13 (s, 9H, C(CH3)3), 2.08 (d, 5J¼1.6 Hz,
tegrated using the program SAINT and the integrated intensities
were corrected for Lorentz-polarization effects with SADABS,
3H, CH3), 3.83 (d, J¼1 Hz, 1H, OCCH), 4.15e4.2 (m, 1H, OCCHCH),
7.05e7.15, 7.25e7.35 (2m, 2 and 3H, respectively, Ph); 13C NMR
m
¼0.076, transmission min¼0.7266, transmission max¼0.9977. The
(75 MHz, CDCl3):
d
11.1, 29 (3C), 36.1, 58.4, 59.5, 127.2 (2C), 127.7,
structure was solved by direct methods and refined to unique F2 by
full matrix least squares. No. of parameters¼192. All of the hydro-
gen atoms were placed at idealized positions and retained as rigid
129.1 (2C), 135, 140.6, 178.4, 203.4; EIMS m/z: 262 (Mþ, 21%), 247
(11), 228 (11), 227 (61), 205 (11), 169 (11), 141 (17), 128 (10), 125

7064
R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
atoms. R¼0.0718, wR¼0.1323, residual electron density¼0.519. All
to unique F2 by full matrix least squares. No. of parameters¼493 All
of the hydrogen atoms were placed at idealized positions and
retained as rigid atoms. R¼0.0718, wR¼0.1323, residual electron
density¼0.161. All results were deposited at Cambridge Crystallo-
graphic Data Centre.
results were deposited at Cambridge Crystallographic Data Centre.
4.3.24. 2-Butyl-3-phenyl-1H-cyclopenta[a]naphthalen-1-one
(10b). Orange oil; Rf¼0.6 (hexane/ethyl acetate 4:1); tR 21.8; IR
(cmꢂ1): 1697, 1628, 1579, 1518, 1492, 1441, 1367, 1334, 1158, 1088,
1049, 1023, 827, 799, 744, 698; 1H NMR (300 MHz, CDCl3):
d
0.85 (t,
4.3.27. (E)-2-Butyl-3-butylidene-2,3-dihydro-1H-cyclopenta[a]
naphthalen-1-one (11b). Orange oil; Rf¼0.57 (hexane/ethyl acetate
4:1); tR 19.1; IR (cmꢂ1): 1693, 1621, 1587, 1514, 1456, 1439, 1184, 821,
J¼7.3 Hz, 3H, CH3), 1.25e1.4, 1.45e1.55 (2m, 2H each one, CH2 ꢁ2),
2.33 (t, J¼7.5 Hz, 2H, CCH2), 7.15 (d, J¼8.1 Hz, 1H, OCCCCHCHC), 7.29
(ddd, J¼8.3 and 6.8 Hz, 4J¼1.2 Hz, 1H, OCCCCHCHCH), 7.4e7.55 (m,
6H, Ph and OCCCCHCHCH), 7.65 (d, J¼8.4 Hz, 1H, OCCCCCHCHCH),
7.74 (d, J¼8.1 Hz, 1H, OCCCCHCHC), 8.73 (dd, J¼8.3 Hz, 4J¼0.9 Hz,
750; 1H NMR (300 MHz, CDCl3):
d
0.83, 1.05 (2t, J¼7 and 7.4 Hz,
respectively, 3H each one, CH3 ꢁ2), 1.2e1.35, 1.55e1.65 (2m, 4 and
2H, respectively, CH2 ꢁ3), 1.85e1.95, 2.05e2.15 (2m, 1H each one,
OCCHCH2), 2.25e2.45 (m, 2H, OCCHCCHCH2), 3.3e3.4 (m 1H,
OCCH), 6.36 (td, J¼7.6 Hz, 4J¼1.5 Hz, 1H, OCCHCCH), 7.55 (t,
J¼7.5 Hz, 1H, OCCCCHCHCH), 7.68 (t, J¼7.5 Hz, 1H, OCCCCHCHCH),
7.78 (d, J¼8.6 Hz, 1H, OCCCCHCHC), 7.88 (d, J¼8.2 Hz, 1H,
OCCCCCHCHCH), 8.03 (d, J¼8.6 Hz, 1H, OCCCCHCHC), 9.19 (d,
1H, OCCCCHCHCH); 13C NMR (75 MHz, CDCl3):
d 13.8, 22.8, 22.9,
31.6, 118.9, 122.5, 123.5, 125.5, 127.7 (2C), 128.3, 128.7 (2C), 128.9,
129, 129.1, 132.9, 133.8, 134.1, 134.3, 147.2, 153.1, 200.3; EIMS m/z:
313 (Mþþ1, 20%), 312 (Mþ, 80), 271 (10), 270 (47), 269 (100), 268
(10), 257 (13), 256 (19), 252 (18), 251 (14), 250 (12), 241 (20), 240
(21), 239 (63), 226 (12). HRMS calcd for C23H20O: 312.1514; found:
312.1470.
J¼8.4 Hz, 1H, OCCCCHCHCH); 13C NMR (75 MHz, CDCl3):
d 13.8, 14,
22.8, 23, 26.9, 30.9, 31.6, 49.6, 118.1, 124.9, 125.8, 126.6, 128.1, 129.1,
129.2, 129.5, 133.1, 135.7, 136.7, 152.8, 207.1; EIMS m/z: 292 (Mþ,
23%), 250 (23), 249 (17), 237 (19), 236 (100), 221 (19), 209 (11), 208
(63), 207 (28), 194 (32), 191 (12), 189 (11), 179 (31), 178 (39), 165
(26), 152 (11). HRMS calcd for C21H24O: 292.1827; found: 292.1807.
4.3.25. 2-Methyl-3-(p-tolyl)-1H-cyclopenta[a]naphthalen-1-one
(10c). Brown oil; Rf¼0.5 (hexane/ethyl acetate 4:1); tR 20.9; IR
(cmꢂ1): 1697, 1621, 1580, 1509, 1439, 1377, 1329, 1239, 1187, 1158,
1064, 913, 825, 811, 757; 1H NMR (300 MHz, CDCl3):
d 1.93 (s, 3H,
OCCCH3), 2.45 (s, 3H, CHCCH3), 7.29 (d, J¼8.1 Hz, 1H, OCCCCHCHC),
7.3e7.35 (m, 3H, CH3CCH ꢁ2 and OCCCCHCHCH), 7.42 (d, J¼8.2 Hz,
2H, CH3CCHCH ꢁ2), 7.50 (ddd, J¼8.5 and 6.8 Hz, 4J¼1.3 Hz, 1H,
OCCCCHCHCH), 7.7 (d, J¼8.5 Hz, 1H, OCCCCCHCHCH), 7.81 (d,
J¼8.1 Hz, 1H, OCCCCHCHC), 8.75 (dd, J¼8.5 Hz, 4J¼1.3 Hz, 1H,
4.3.28. (E)-2-Pentyl-3-pentylidene-2,3-dihydro-1H-cyclopenta[a]
naphthalen-1-one (11c). Pale yellow oil; Rf¼0.67 (hexane/ethyl ac-
etate 4:1); tR 21; IR (cmꢂ1): 1693, 1620, 1587, 1515, 1457, 1439, 1183,
822, 751; 1H NMR (300 MHz, CDCl3):
d
0.8, 0.96 (2t, J¼6.9 and
7.2 Hz, respectively, 3H each one, CH3 ꢁ2), 1.1e1.35, 1.4e1.45,
1.5e1.55 (3m, 6, 2 and 2H, respectively, CH2 ꢁ5), 1.8e1.9, 2.05e2.15
(2m, 1H each one, OCCHCH2), 2.3e2.4 (m, 2H, OCCHCCHCH2),
3.25e3.35 (m 1H, OCCH), 6.33 (dt, J¼7.6 Hz, 4J¼1.5 Hz, 1H,
OCCHCCH), 7.53 (ddd, J¼8.1 and 7.1 Hz, 4J¼1.2 Hz, 1H,
OCCCCHCHCH), 7.65 (ddd, J¼8.3 and 7.1 Hz, 4J¼1.2 Hz, 1H,
OCCCCHCHCH), 7.76 (d, J¼8.7 Hz, 1H, OCCCCHCHC), 7.85 (d,
J¼8.1 Hz, 1H, OCCCCCHCHCH), 8.01 (d, J¼8.7 Hz, 1H, OCCCCHCHC),
9.15 (d, J¼8.3 Hz, 1H, OCCCCHCHCH); 13C NMR (75 MHz, CDCl3):
OCCCCHCHCH); 13C NMR (75 MHz, CDCl3):
d 8.5, 21.5, 118.9, 123,
123.7, 125.6, 128 (2C), 128.3, 129, 129.2, 129.4, 129.5, 129.4 (2C),
129.5, 129.9, 133.7, 134, 139.2, 147.3, 153, 200.4; EIMS m/z: 285
(Mþþ1, 23%), 284 (Mþ, 100), 283 (29), 269 (38), 255 (12), 252 (10),
241 (18), 240 (15), 239 (37), 207 (17), 119 (11). HRMS calcd for
C21H16O: 284.1201; found: 284.1237.
4.3.26. (E)-2-Ethyl-3-ethylidene-2,3-dihydro-1H-cyclopenta[a]naph-
thalen-1-one (11a). Pale yellow solid; mp 94e96 ꢀC; Rf¼0.5 (hex-
ane/ethyl acetate 4:1); tR 16.8; IR (cmꢂ1): 1687, 1620, 1587, 1513,
d
14 (2C), 22.4, 22.6, 24.4, 29.3, 31.2, 31.7, 32.1, 49.6, 118.1, 124.9,
126.1,126.6,128.1,129.1,129.2,129.5,133.1,135.7,136.6,152.8, 207.1;
EIMS m/z: 320 (Mþ, 17%), 264 (19), 263 (18), 251 (12), 250 (60), 249
(10), 221 (14), 209 (18), 208 (100), 207 (24), 195 (12), 194 (31), 191
(14), 189 (13), 182 (23), 179 (35), 178 (46), 165 (29), 152 (11). HRMS
calcd for C23H28O: 320.2140; found: 320.2159.
1440, 1186, 815, 748; 1H NMR (300 MHz, CDCl3):
d
0.81 (t, J¼7.5 Hz,
3H, CH2CH3), 1.95e2.05 (m with d at 2, J¼7.2 Hz, 1 and 3H, re-
spectively, CH2CH3 and CHCH3), 2.15e2.25 (m, 1H, CH2CH3),
3.3e3.35 (m 1H, CHCH2CH3), 6.45 (qd, J¼7.2 Hz, 4J¼1.6 Hz, 1H,
CHCH3), 7.54 (ddd, J¼8.1 and 7 Hz, 4J¼1.3 Hz, 1H, OCCCCHCHCH),
7.68 (ddd, J¼8.4 and 7 Hz, 4J¼1.4 Hz, 1H, OCCCCHCHCH), 7.75 (d,
J¼8.6 Hz, 1H, CH3CHCCCH), 7.87 (d, J¼8.1 Hz, 1H, OCCCCCHCHCH),
8.01 (d, J¼8.6 Hz, 1H, CH3CHCCCHCH), 9.19 (d, J¼8.4 Hz, 1H,
4.3.29. 1,1,2,3-Tetramethylphenanthren-4-(1H)-one (12). Pale yel-
low oil; Rf¼0.53 (hexane/ethyl acetate 4:1); tR 17.1; IR (cmꢂ1): 1701,
1633, 1616, 1595, 1508, 1457, 1378, 1284, 1071, 827, 757; 1H NMR
OCCCCHCHCH); 13C NMR (75 MHz, CDCl3):
d
9.2, 15.1, 23.7, 50.2,
(300 MHz, CDCl3):
d
1.54 (s, 6H, C(CH3)2), 2.09 (q, 5J¼0.8 Hz, 3H,
117.9, 120.3, 124.8, 126.6, 128, 129, 129.1, 129.5, 133, 135.7, 137.2,
152.9, 207; EIMS m/z: 236 (Mþ, 36%), 209 (17), 208 (100), 193 (16),
179 (21), 178 (42), 165 (22). HRMS calcd for C17H16O: 236.1201;
found: 236.1179. Crystal data: C17H16O, M¼236.30; Crystal size
OCCCH3), 2.11 (q, 5J¼0.8 Hz, 3H, OCCCCH3), 7.53 (ddd, J¼8.1 and
6.8 Hz, 4J¼1.2 Hz, 1H, OCCCCHCHCH), 7.64 (ddd, J¼8.3 and 6.8 Hz,
4J¼1.6 Hz, 1H, OCCCCHCHCH), 7.67 (d, J¼8.8 Hz, 1H, OCCCCHCHC),
7.83 (d, J¼8 Hz, 1H, OCCCCCHCHCH), 7.99 (d, J¼8.8 Hz, 1H,
OCCCCHCHC), 9.79 (d, J¼8.3 Hz, 1H, OCCCCHCHCH); 13C NMR
max¼0.16, mid¼0.14, min¼0.04; Triclinic, space group P1, a¼5.268
(4), b¼7.674 (6), c¼25.24 (2) A,
a
¼86.224ꢀ (13),
b
¼84.914ꢀ (14),
(75 MHz, CDCl3): d 12.3, 16.7, 28 (2C), 40.8, 124, 124.7, 126.1, 127.7,
ꢁ
3
g
¼71.474ꢀ (14); V¼9630 (13) A ; rcalcd¼1.222 g/cm3; 2qmax¼50.1;
127.9, 128.4, 131.1, 132, 132.3, 133, 152.4, 155.1, 186.8; EIMS m/z: 251
(Mþþ1, 20%), 250 (Mþ, 100), 236 (16), 235 (85), 222 (19), 221 (11),
220 (19), 209 (36), 208 (21), 207 (90), 193 (10), 192 (54), 191 (36),
190 (13), 189 (21), 179 (14), 178 (15), 166 (12), 165 (27), 152 (14).
HRMS calcd for C18H18O: 250.1358; found: 250.1345.
ꢁ
ꢁ
radiation type: Mo,
scan runs (starting
l
¼0.71073 A; data collection based on three
u-
u
¼ꢂ34ꢀ) at values
F
¼0ꢀ, 120ꢀ, 240ꢀ with the
detector at 2
u
q
¼ꢂ32ꢀ. An additional run of 100 frames, at 2
q
¼ꢂ32ꢀ,
¼ꢂ34ꢀ and
F
¼0ꢀ, was acquiredto improveredundancy. Foreach of
these runs, 606 frames were collected at 0.3ꢀ intervals and 30 s per
frame. T¼24ꢃ1 ꢀC, measured and independent reflections¼6371,
4.4. General procedure for the synthesis of furans
reflections included in refinement¼8052, I>2/
s. The diffraction
frames were integrated using the program SAINTand the integrated
intensities were corrected for Lorentz-polarization effects with
To a stirred solution of alkyne (2, 1 mmol) in dry toluene
(2.5 mL) under argon atmosphere were added Fe3O4 (25 mg) and
the corresponding acid chloride (1, 1.5 mmol). The resulting mix-
ture was stirred at 70 ꢀC during an hour. The catalyst was removed
SADABS,
m
¼0.074, transmission min¼0.828, transmission
max¼0.997. The structure was solved by direct methods and refined

R. Cano et al. / Tetrahedron 69 (2013) 7056e7065
7065
by a magnet and IrO2eFe3O4 (25 mg) was added. The mixture was
stirred at 130 ꢀC during three days. The catalyst was removed by
a magnet and the resulting mixture was quenched with water
(5 mL) and extracted with EtOAc (3ꢁ5 mL). The organic phases
were dried over MgSO4, followed by evaporation under reduced
pressure to remove the solvent. The product was usually purified by
chromatography on silica gel (hexane/ethyl acetate) to give the
corresponding furans 13. Physical and spectroscopic data, as well as
literature for known compound, follow:
1.35e1.5, 1.55e1.7, 1.7e1.8 (3m, 2H each one, CH2 ꢁ3), 2.55-2.7 (m,
4H, CCH2 ꢁ2), 6 (s, 1H, OCCHC), 7.08 (dd, J¼5 and 3.7 Hz, 1H,
SCHCH), 7.2 (dd, J¼3.7 Hz, 4J¼1.1 Hz, 1H, SCCH), 7.23 (dd, J¼5 Hz,
4J¼1.1 Hz, 1H, SCH); 13C NMR (75 MHz, CDCl3):
d 13.8, 13.9, 21.4,
22.6, 25.5, 30.1, 31.9, 108.7, 121.8, 122.1, 123, 127.2, 134.3, 142.7,
154.8; EIMS m/z: 249 (Mþþ1, 10%), 248 (Mþ, 57), 220 (15), 219
(100), 205 (29), 111 (27). HRMS calcd for C15H20OS: 248.1235;
found: 248.1228.
Acknowledgements
4.4.1. 3-Butyl-2-phenyl-5-propylfuran (13a). Pale yellow oil;
Rf¼0.77 (hexane/ethyl acetate 4:1); tR 14.3; IR (cmꢂ1): 1600, 1554,
1492, 1463, 1457, 1446, 801, 762, 692; 1H NMR (300 MHz, CDCl3):
This work was supported by the current Spanish Ministerio de
Economía y Competitividad (Consolider Ingenio 2010 CSD2007-
00006 and CTQ2011-24151) and the Generalitat Valenciana (G.V.;
PROMETEO 2009/03, FEDER). R.C. thanks to G.V. for a fellowship
through the PROMETEO program. We gratefully acknowledge the
polishing of our English by Mrs. Oriana C. Townley.
d
1.01 (t, J¼7.3 Hz, 3H, CCH2CH2CH2CH3), 1.06 (t, J¼7.4 Hz, 3H,
CCH2CH2CH3), 1.48 (h, J¼7.3 Hz, 2H, CCH2CH2CH2CH3), 1.6e1.7 (m,
2H, CCH2CH2CH2CH3), 1.77 (h, J¼7.4 Hz, 2H, CCH2CH2CH3), 2.68,
2.69 (2t, J¼7.4 Hz each one, 2H each one, CCH2 ꢁ2), 6.04 (s, 1H,
OCCHC), 7.27 (t, J¼7.4 Hz, 1H, OCCCHCHCH), 7.44 (t, J¼7.4 Hz, 2H,
OCCCHCH ꢁ2), 7.64 (d, 2H, J¼7.4 Hz, 2H, OCCCH ꢁ2); 13C NMR
Supplementary data
(75 MHz, CDCl3):
d 13.8, 14, 21.4, 22.7, 25.7, 30.1, 32.2, 109, 122.4,
125.2 (2C), 126.2, 128.4 (2C), 132.3, 146.4, 154.9; EIMS m/z: 243
(Mþþ1, 10%), 242 (Mþ, 55), 214 (17), 213 (100), 200 (11), 199 (20),
105 (25), 77 (20). HRMS calcd for C17H22O: 242.1671; found:
242.1691.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.06.041. These data include MOL files
and InChiKeys of the most important compounds described in this
article.
4.4.2. 3-Ethyl-5-methyl-2-phenylfuran (13b).16 Colorless oil; Rf
¼0.63 (hexane/ethyl acetate 4:1); tR 11.8; IR (cmꢂ1): 1600, 1557,
References and notes
1492, 1444, 1071, 996, 761, 692; 1H NMR (300 MHz, CDCl3):
d 1.26 (t,
J¼7.5 Hz, 3H, CH2CH3), 2.36 (s, 3H, CCH3), 2.68 (q, J¼7.5 Hz, 2H,
1. (a) Gooben, L. J.; Rodríguez, N.; Gooben, K. Angew. Chem., Int. Ed. 2009, 48,
9592e9594; (b) Fujihara, T.; Iwai, T.; Terao, J.; Tsuji, Y. Synlett 2010, 2537e2548.
2. Pohland, A. E.; Benson, W. R. Chem. Rev. 1964, 64, 161e197.
3. (a) Price, C. C.; Pappalardo, J. A. J. Am. Chem. Soc. 1950, 72, 2613e2615; (b)
Benson, W. R.; Pohland, A. E. J. Org. Chem. 1964, 29, 385e391; (c) Martens, H.;
Janssens, F.; Hoornaert, G. Tetrahedron 1975, 31, 177e183; (d) Snelders, D. J. M.;
Dyson, P. J. Org. Lett. 2011, 13, 4048e4051.
CH2CH3), 6.03 (s, 1H, OCCHC), 7.2e7.3, 7.35e7.45, 7.55e7.65 (3m, 2,
2 and 1H, Ph); 13C NMR (75 MHz, CDCl3):
d 13.6, 14.5, 19.2, 109.2,
124, 125.2 (2C), 126.2, 128.4 (2C), 132.1, 146.3, 150.7; EIMS m/z: 187
(Mþþ1, 14%), 186 (Mþ, 100), 172 (11), 171 (87), 143 (18), 128 (31), 115
(11), 105 (13), 77 (21).
4. Manoiu, D.; Manoiu, M.; Dinulescu, I. G.; Avram, M. Rev. Roum. Chim. 1985, 30,
223e227.
4.4.3. 3-Butyl-2-(4-chlorophenyl)-5-propylfuran (13c). Pale yellow
oil; Rf¼0.83 (hexane/ethyl acetate 4:1); tR 15.3; IR (cmꢂ1): 1568,
5. Zhou, H.; Zeng, C.; Ren, L.; Liao, W.; Huang, X. Synlett 2006, 3504e3506.
6. Hosseini-Savari, M.; Mardaneh, Z. Bull. Chem. Soc. Jpn. 2011, 84, 778e782.
7. (a) Kokubo, K.; Matsumasa, K.; Miura, M.; Nomura, M. J. Org. Chem. 1996, 61,
6941e6946; (b) Hua, R.; Shimada, S.; Tanaka, M. J. Am. Chem. Soc. 1998, 120,
12365e12366; (c) Hua, R.; Onozawa, S.-y.; Tanaka, M. Chem.dEur. J. 2005, 11,
3621e3630; (d) Kashiwabara, T.; Kataoka, K.; Hua, R.; Shimada, S.; Tanaka, M.
Org. Lett. 2005, 7, 2241e2244; (e) Kashiwabara, T.; Fuse, K.; Hua, R.; Tanaka, M.
Org. Lett. 2008, 10, 5469e5472; (f) Kashiwabara, T.; Tanaka, M. Adv. Synth. Catal.
2011, 353, 1485e1490.
8. (a) Iwai, T.; Fujihara, T.; Terao, J.; Tsuji, Y. J. Am. Chem. Soc. 2009, 131,
6668e6669; (b) Iwai, T.; Fujihara, T.; Terao, J.; Tsuji, Y. J. Am. Chem. Soc. 2012,
134, 1268e1274.
9. Wang, B.; Wang, S.; Li, P.; Wang, L. Chem. Commun. 2010, 5891e5893.
10. Gandeepan, P.; Parthasarathy, K.; Su, T.-H.; Cheng, C.-H. Adv. Synth. Catal. 2012,
354, 457e468.
1549, 1487, 1464, 1094, 828; 1H NMR (300 MHz, CDCl3):
d 0.97, 1.03
(2t, J¼7.2 and 7.3 Hz, respectively, 3H each one, CH3 ꢁ2), 1.35e1.5,
1.55e1.65, 1.7e1.8 (3m, 2H each one, CH2 ꢁ3), 2.62, 2.64 (2t, J¼7.4
and 7.3 Hz, respectively, 2H each one, CCH2 ꢁ2), 6.01 (s, 1H,
OCCHC), 7.37 (d, J¼8.7 Hz, 2H, ClCCH ꢁ2), 7.53 (d, J¼8.7 Hz, 2H,
ClCCHCH ꢁ2); 13C NMR (75 MHz, CDCl3):
d 13.8, 13.9, 21.4, 22.6,
25.7, 30.1, 32.1, 109.1, 123, 126.3 (2C), 128.6 (2C), 130.7, 131.7, 145.4,
155.2; EIMS m/z: 277 (Mþþ1, 22%), 276 (Mþ, 100), 255 (11), 253
(35), 137 (12). HRMS calcd for C17H21ClO: 276.1281; found:
276.1214.
ꢀ
ꢀ
11. (a) Martínez, R.; Ramon, D. J.; Yus, M. Adv. Synth. Catal. 2008, 350, 1235e1240;
(b) Martínez, R.; Ramon, D. J.; Yus, M. Org. Biomol. Chem. 2009, 7, 2176e2181; (c)
Cano, R.; Ramon, D. J.; Yus, M. Synlett 2011, 2017e2020.
12. (a) Aliaga, M. J.; Ramon, D. J.; Yus, M. Org. Biomol. Chem. 2010, 8, 43e46; (b)
ꢀ
4.4.4. 3-Butyl-2-(4-methoxyphenyl)-5-propylfuran
(13d). Yellow
oil; Rf¼0.63 (hexane/ethyl acetate 4:1); tR 16; IR (cmꢂ1): 1606, 1577,
ꢀ
ꢀ
Cano, R.; Ramon, D. J.; Yus, M. J. Org. Chem. 2010, 75, 3458e3460; (c) Cano, R.;
1559, 1505, 1462, 1293, 1247, 1176, 1037, 830, 801; 1H NMR
ꢀ
ꢀ
Ramon, D. J.; Yus, M. Tetrahedron 2011, 67, 5432e5436; (d) Cano, R.; Ramon, D.
ꢀ
(300 MHz, CDCl3):
d
1.01, 1.07 (2t, J¼7.3 and 7.4 Hz, respectively, 3H
J.; Yus, M. J. Org. Chem. 2011, 76, 5547e5557; (e) Cano, R.; Yus, M.; Ramon, D. J.
Tetrahedron 2011, 67, 8079e8085; (f) Cano, R.; Yus, M.; Ramon, D. J. Tetrahedron
2012, 68, 1393e1400; (g) Cano, R.; Yus, M.; Ramon, D. J. Chem. Commun. 2012,
7628e7630; (h) Perez, J. M.; Cano, R.; Yus, M.; Ramon, D. J. Eur. J. Org. Chem.
ꢀ
each one, CH2CH3 ꢁ2), 1.4e1.55, 1.6e1.7, 1.7e1.85 (3m, 2H each one,
CH2 ꢁ3), 2.65, 2.68 (2t, J¼7.2 and 7.3 Hz, respectively, 2H each one,
CCH2 ꢁ2), 3.87 (s, 3H, OCH3), 6.03 (s, 1H, OCCHC), 7 (d, J¼9 Hz, 2H,
OCCHCH ꢁ2), 7.58 (d, J¼9 Hz, 2H, OCCHCH ꢁ2); 13C NMR (75 MHz,
ꢀ
ꢀ
ꢀ
2012, 4548e4554.
13. (a) Denmark, S. E. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Paquette, L. A., Eds.; Pergamon: Oxford, UK, 1991; Vol. 5, pp 751e784; (b)
Habermas, K. L.; Denmark, S. E.; Jones, T. K. In Organic Reactions; Paquette, L. A.,
Ed.; John Wiley & Sons: New York, NY, 1994; Vol. 45, pp 1e158; (c) Vaidya, T.;
Eisenberg, R.; Frontier, A. J. ChemCatChem 2011, 3, 1531e1548.
14. (a) Martin, G. J.; Rabiller, C.; Mabon, G. Tetrahedron Lett. 1970, 3131e3132; (b)
Martin, G. J.; Rabiller, C.; Mabon, G. Tetrahedron 1972, 28, 4027e4037; (c) Rizzo,
C. J.; Dunlap, N. K.; Smith, A. B. J. Org. Chem. 1987, 52, 5280e5283; (d)
Fiandanese, V.; Marchese, G.; Punzi, A.; Ruggieri, G. Tetrahedron Lett. 1996, 37,
8455e8458.
CDCl3): d 13.8, 13.9, 21.4, 22.6, 25.6, 30.1, 32.3, 55.1, 108.6, 113.9 (2C),
120.7, 125.2, 126.7 (2C), 146.4, 154.2, 158.1; EIMS m/z: 273 (Mþþ1,
13%), 272 (Mþ, 66), 244 (17), 243 (100), 229 (21), 135 (13). HRMS
calcd for C18H24O2: 272.1776; found: 272.1742.
4.4.5. 3-Butyl-5-propyl-2-(thiophen-2-yl)furan (13e). Pale yellow
oil; Rf¼0.8 (hexane/ethyl acetate 4:1); tR 14.4; IR (cmꢂ1): 1566,
1464, 1378, 1258, 976, 848, 821, 687; 1H NMR (300 MHz, CDCl3):
15. Lee, K. Y.; Lee, M. J.; Kim, J. N. Tetrahedron 2005, 61, 8705e8710.
16. Danheiser, R. L.; Stoner, E. J.; Koyama, H.; Yamashita, D. S.; Klade, C. A. J. Am.
Chem. Soc. 1989, 111, 4407e4413.
d
0.99,1.03 (2t, J¼6.5 and 6.6 Hz, respectively, 3H each one, CH3 ꢁ2),